Despite improvements in antibiotics, surgical techniques, and intensive care support, sepsis and shock, especially following surgery, continues to pose a significant problem. Stimulation of the reticuloendothelial system (RES) offers one additional mode of therapy for shock and sepsis. We have demonstrated that zymosan and glucan offer marked protection against experimental peritonitis. The availability of the highly purified glucan preparation offers hope that this agent may be used as a clinical reticuloendothelial stimulant. We are in the process of developing a new RES function test using Indium labeled E. coli. This will allow for the direct measurement of RES function and on the effect of RES stimulants. To help identify the mechanism of RES stimulation, Cynomolgus monkeys pretreated with glucan will be subjected to shock with live E. coli infusion. In vivo phagocytic clearance studies, complement levels, lysozymosal enzyme levels and fibronectin levels will be measured. Hopefully, by the measurement of these various substances we will be delineate the role that specific mechanisms of action of RES stimulants. In addition, we will further evaluate the mechanism of N-Formyl peptides as chemotaxins. We have demonstrated that dog granulocytes as opposed to rabbit and human granulocytes do not appear to have a receptor for N-Formyl. These are granulocytes, however chemotax normally towards bacterial filtrates. Knowledge of this may allow for further delineation of the effects of informal peptides. Our goal then is to develop an understanding of the mechanism of action of the RES stimulation and to further delineate agents that may be useful clinically.